Serum glutamine, set-shifting ability and anorexia nervosa

Michiko Nakazato,Iain C Campbell,Janet Treasure,David A Collier,Kate Tchanturia,Kenji Hashimoto,Masaomi Iyo,Ulrike Schmidt

doi:10.1186/1744-859x-9-29

Abstract

BackgroundSet-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological and biochemical processes are unclear. Animal studies have established that glutamatergic pathways in the prefrontal cortex play an important role in set-shifting ability. However, it is not yet understood whether levels of serum glutamatergic amino acids are associated with set-shifting performance in humans. The aim of this study was to determine whether serum concentrations of amino acids related to glutamatergic neurotransmission (glutamine, glutamate, glycine, l-serine, d-serine) are associated with set-shifting ability in people with acute AN and those after recovery.MethodsSerum concentrations of glutamatergic amino acids were measured in 27 women with current AN (AN group), 18 women recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST) and the Trail Making Task (TMT). Dimensional measures of psychopathology were used, including the Eating Disorder Examination Questionnaire (EDEQ), the Maudsley Obsessive-Compulsive Inventory (MOCI) and the Hospital Anxiety and Depression Scale (HADS).ResultsSerum glutamine concentrations in the AN group (1,310.2 ± 265.6 μM, mean ± SD) were significantly higher (by approximately 20%) than those in the HC group (1,102.9 ± 152.7 μM, mean ± SD) (F(2, 70) = 6.3, P = 0.003, 95% CI 61.2 to 353.4). Concentrations of serum glutamine were positively associated with markers of the illness severity: a negative correlation was present between serum glutamine concentrations and body mass index (BMI) and lowest BMI and a positive correlation was found between duration of illness and EDEQ. The AN group showed significantly impaired set shifting in the WCST, both total errors, and perseverative errors. In the AN group, there were no correlations between serum glutamine concentrations and set shifting.ConclusionsSerum concentrations of glutamine may be a biomarker of illness severity in people with AN. It does not appear to be directly associated with changes in executive function.

Highlights

Set-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological and biochemical processes are unclear
This proposal has some indirect support from proton magnetic resonance spectroscopy (MRS) studies, which have reported that people with AN have lower levels of a combined measure of glutamate and glutamine (Glx) and of N-acetyl aspartate (NAA) in the frontal grey matter [14]
The ANRec group showed significantly higher levels of anxiety on Maudsley Obsessive-Compulsive Inventory (MOCI) and Hospital Anxiety and Depression Scale (HADS) anxiety testing compared with the HC group

Summary

Introduction

Set-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological and biochemical processes are unclear. The problem has been identified in bulimia nervosa (BN), schizophrenia [6], bipolar disorder [7] and obsessive-compulsive disorder [8] It appears to Glutamate is the principal excitatory neurotransmitter in brain and is involved in cognitive functions such as memory and learning [11]. It has been proposed that the agerelated decline in set-shifting ability is associated with alterations in glutamate receptor binding in the cingulate cortex and dorsomedial striatum [16] These various studies suggest that the functioning of the glutamatergic system in the prefrontal region may be related to the impaired cognitive performance seen in people with AN and in other psychiatric disorders [17,18]. MRS studies of people with AN [14,15,22,23] have shown heterogenous findings possibly due to methodological factors

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